A chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch.

Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control gamma-to-beta switching, we analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome-i.e., chromosome 11--sufficient for expression of human fetal globin and the subsequent gamma-to-beta switch. The results suggest that the gamma-to-beta switch is controlled either cis to the beta-globin locus or by a trans-acting mechanism, the genes of which reside on human chromosome 11.